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Query: UMLS:C0403608 (
ureter
)
9,655
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
To investigate the role of
myosin light chain kinase
(
MLCK
) in phasic contractions of intact smooth muscle, we have applied Wortmannin, an
MLCK
inhibitor, to strips of guinea-pig
ureter
. Simultaneous measurements of electrical activity, intracellular [Ca2+] ([Ca2+]i) and phasic force showed that Wortmannin (1-4 microM) abolishes force with little or no change in [Ca2+]i and electrical activity. High-K+-induced force production was also abolished by Wortmannin. The effects of Wortmannin were dose dependent - at lower concentrations (100 nM) Wortmannin reduced phasic contractility by 40-50%. It also significantly increased the delay between the Ca2+ peak and force production. These data show that, in phasic smooth muscle, inhibition of
MLCK
causes contraction to fail, despite normal electrical activity and Ca2+ transients. Our results also indicate that Wortmannin has no secondary effects and that other means of producing force, independent of myosin phosphorylation, are negligible in this tissue. The increased lag between the rise of Ca2+ and force production when
MLCK
is inhibited was surprising and suggests that post-phosphorylation steps may play a larger role in the delay than was previously considered.
...
PMID:The effect of inhibition of myosin light chain kinase by Wortmannin on intracellular [Ca2+], electrical activity and force in phasic smooth muscle. 971 16
The
ureter
acts as a functional syncytium and is controlled by a propagating plateau-type action potential (AP) which gives rise to a wave of contraction (ureteral peristalsis) via a process called excitation-contraction (E-C)coupling. The second messenger Ca
2+
activates Ca
2+
/calmodulin-dependent
myosin light chain kinase
-dependent phosphorylation of 20-kDa regulatory light chains of myosin which leads to ureteric contraction. Ca
2+
entry from the extracellular space via voltage-gated L-type Ca
2+
channels (VGCCs) provides the major source of activator Ca
2+
, responsible for generation of both the AP and a Ca
2+
transient that appears as an intercellular Ca
2+
wave. The AP, inward Ca
2+
current, Ca
2+
transient and twitch contraction are all fully blocked by the selective L-type Ca
2+
channel blocker nifedipine. Ca
2+
entry via VGCCs, coupled to activation of Ca
2+
-sensitive K
+
(K
Ca
) or Cl
-
(Cl
Ca
) channels, acts as a negative or positive feedback mechanism, respectively, to control excitability and the amplitude and duration of the plateau component of the AP, Ca
2+
transient and twitch contraction. The
ureter
, isolated from the pelvis, is not spontaneously active. However, spontaneous activity can be initiated in the proximal and distal
ureter
by a variety of biological effectors such as neurotransmitters, paracrine, endocrine and inflammatory factors. Applied agonists depolarise ureteric smooth muscles cells to threshold of AP activation, initiating propagating intercellular AP-mediated Ca
2+
waves to produce antegrade and/or retrograde ureteric peristalsis. Several mechanisms have been proposed to describe agonist-induced depolarization of ureteric smooth muscle, which include suppression of K
+
channels, stimulation of Cl
Ca
current and activation of non-selective cation receptor/store operated channels.
...
PMID:Excitation-Contraction Coupling in Ureteric Smooth Muscle: Mechanisms Driving Ureteric Peristalsis. 3118 24
